US2023312561A1PendingUtilityA1
Solid forms of (z)-methyl 3-(((4-(n-methyl-2-(4-methylpiperazin-1-yl)acetamido)phenyl)amino)(phenyl)methylene)-2-oxo-2,3-dihydro-1h-pyrrolo[2,3-b]pyridine-6-carboxylate and salts thereof
Est. expiryJul 1, 2040(~13.9 yrs left)· nominal 20-yr term from priority
A61P 13/00A61P 9/00C07D 471/04C07B 2200/13A61K 9/48A61K 31/496
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Claims
Abstract
The present disclosure provides crystalline solid forms of an antifibrotic agent, pharmaceutical compositions comprising the same, and methods of use thereof.
Claims
exact text as granted — not AI-modified1 . A solid form of Compound 2:
wherein X is hydrochloric acid, maleic acid, methanesulfonic acid, or p-toluenesulfonic acid.
2 . The solid form according to claim 1 , wherein X is hydrochloric acid.
3 . The solid form according to claim 2 , wherein the solid form is crystalline.
4 . The solid form according to claim 3 , wherein the solid form is a hydrate.
5 . The solid form according to claim 4 , wherein the solid form is characterized by one or more peaks in its XRPD pattern selected from those at about 5.28, 10.63, 11.54, 17.05, and 20.98 degrees 2-theta.
6 . The solid form according to claim 4 , wherein the solid form is characterized by peaks in its XRPD pattern at about 5.28, 10.63, 11.54, 17.05, and 20.98 degrees 2-theta, corresponding to d-spacing of about 16.74, 8.33, 7.67, 5.20, and 4.23 angstroms, respectively.
7 . The solid form according to claim 4 , wherein the solid form is characterized by substantially all of the peaks (degrees 2-theta) in its XRPD pattern selected from
°2θ ± 0.2
5.28
5.76
10.63
11.54
12.73
13.13
14.08
15.34
15.64
16.00
16.55
17.05
17.78
18.86
19.08
20.16
20.68
20.98
21.62
22.05
22.82
23.97
24.94
25.23
25.61
26.58
27.01
27.78
29.89
30.51
30.91
31.72
33.39
8 . The solid form according to claim 4 , wherein the solid form is characterized by one or more of the following:
(i) an XRPD pattern substantially similar to that depicted in FIG. 5 ; (ii) a TGA pattern substantially similar to that depicted in FIG. 6 ; and (iii) a DSC pattern substantially similar to that depicted in FIG. 6 .
9 . The solid form according to claim 4 , wherein the solid form is characterized by one or more peaks in its XRPD pattern selected from those at about 6.02, 10.07, 10.46, 13.02, and 14.99 degrees 2-theta.
10 . The solid form according to claim 4 , wherein the solid form is characterized by peaks in its XRPD pattern at about 6.02, 10.07, 10.46, 13.02, and 14.99 degrees 2-theta, corresponding to d-spacing of about 14.68, 8.78, 8.46, 6.80, and 5.91 angstroms, respectively.
11 . The solid form according to claim 4 , wherein the solid form is characterized by substantially all of the peaks (degrees 2-theta) in its XRPD pattern selected from
°2θ ± 0.2
6.02
10.07
10.46
13.02
14.13
14.99
15.35
16.27
17.65
18.17
18.88
19.63
20.27
20.90
22.41
23.96
24.37
25.45
26.22
26.82
27.90
28.61
29.66
30.30
31.04
31.72
32.91
34.13
12 . The solid form according to claim 4 , wherein the solid form is characterized by one or more of the following:
(i) an XRPD pattern substantially similar to that depicted in FIG. 7 ; (ii) a TGA pattern substantially similar to that depicted in FIG. 8 ; and (iii) a DSC pattern substantially similar to that depicted in FIG. 8 .
13 . The solid form according to claim 3 , wherein the solid form is an anhydrate.
14 . The solid form according to claim 13 , wherein the solid form is characterized by one or more peaks in its XRPD pattern selected from those at about 5.29, 7.44, 9.38, 14.29, and 14.76 degrees 2-theta.
15 . The solid form according to claim 13 , wherein the solid form is characterized by peaks in its XRPD pattern at about 5.29, 7.44, 9.38, 14.29, and 14.76 degrees 2-theta, corresponding to d-spacing of about 16.70, 11.88, 9.43, 6.20, and 6.00 angstroms, respectively.
16 . The solid form according to claim 13 , wherein the solid form is characterized by substantially all of the peaks (degrees 2-theta) in its XRPD pattern selected from
°2θ ± 0.2
5.29
7.44
9.38
9.75
10.51
12.97
14.29
14.76
15.66
16.61
16.84
17.26
17.81
18.48
18.87
19.05
19.41
19.90
20.72
21.50
22.38
23.44
24.01
24.73
25.85
26.50
27.44
27.93
28.74
30.04
30.99
32.41
33.89
17 . The solid form according to claim 13 , wherein the solid form is characterized by one or more of the following:
(i) an XRPD pattern substantially similar to that depicted in FIG. 9 ; (ii) a TGA pattern substantially similar to that depicted in FIG. 10 ; and (iii) a DSC pattern substantially similar to that depicted in FIG. 10 .
18 . The solid form according to claim 4 , wherein the solid form is characterized by one or more peaks in its XRPD pattern selected from those at about 5.29, 9.37, 9.73, 15.29, 21.60, and 23.71 degrees 2-theta.
19 . The solid form according to claim 4 , wherein the solid form is characterized by peaks in its XRPD pattern at about 5.29, 9.37, 9.73, 15.29, 21.60, and 23.71 degrees 2-theta, corresponding to d-spacing of about 16.72, 9.44, 9.09, 5.80, 4.12, and 3.75 angstroms, respectively.
20 . The solid form according to claim 4 , wherein the solid form is characterized by substantially all of the peaks (degrees 2-theta) in its XRPD pattern selected from
°2θ ± 0.2
5.29
9.37
9.73
14.16
15.29
15.99
17.35
18.94
19.30
19.59
19.82
20.26
20.89
21.60
22.99
23.39
23.71
24.94
25.70
26.50
28.23
28.96
30.28
31.27
32.37
21 . The solid form according to claim 4 , wherein the solid form is characterized by one or more of the following:
(i) an XRPD pattern substantially similar to that depicted in FIG. 11 ; (ii) a TGA pattern substantially similar to that depicted in FIG. 12 ; and (iii) a DSC pattern substantially similar to that depicted in FIG. 12 .
22 . The solid form according to claim 4 , wherein the solid form is characterized by one or more peaks in its XRPD pattern selected from those at about 4.71, 7.78, 10.30, 13.04, and 15.64 degrees 2-theta.
23 . The solid form according to claim 4 , wherein the solid form is characterized by peaks in its XRPD pattern at about 4.71, 7.78, 10.30, 13.04, and 15.64 degrees 2-theta, corresponding to d-spacing of about 18.74, 11.37, 8.59, 6.79, and 5.67 angstroms, respectively.
24 . The solid form according to claim 4 , wherein the solid form is characterized by substantially all of the peaks (degrees 2-theta) in its XRPD pattern selected from
°2θ ± 0.2
4.71
5.61
7.78
9.25
10.30
13.04
14.27
14.88
15.64
16.91
17.67
18.26
20.35
20.69
21.37
22.53
24.20
25.06
25.51
26.31
29.00
29.69
31.28
32.77
25 . The solid form according to claim 4 , wherein the solid form is characterized by one or more of the following:
(i) an XRPD pattern substantially similar to that depicted in FIG. 13 ; (ii) a TGA pattern substantially similar to that depicted in FIG. 14 ; and (iii) a DSC pattern substantially similar to that depicted in FIG. 14 .
26 . The solid form according to claim 13 , wherein the solid form is characterized by one or more peaks in its XRPD pattern selected from those at about 6.19, 9.70, 12.09, 16.00, and 20.05 degrees 2-theta.
27 . The solid form according to claim 13 , wherein the solid form is characterized by peaks in its XRPD pattern at about 6.19, 9.70, 12.09, 16.00, and 20.05 degrees 2-theta, corresponding to d-spacing of about 14.28, 9.12, 7.32, 5.54, and 4.43 angstroms, respectively.
28 . The solid form according to claim 13 , wherein the solid form is characterized by substantially all of the peaks (degrees 2-theta) in its XRPD pattern selected from
°2θ ± 0.2
5.27
6.19
7.30
9.70
10.65
12.09
12.62
14.41
16.00
16.50
16.83
18.73
19.50
20.05
20.71
21.24
21.49
21.95
22.68
23.08
23.71
24.62
25.74
26.89
27.85
28.92
29.88
30.87
31.53
32.49
33.96
29 . The solid form according to claim 13 , wherein the solid form is characterized by one or more of the following:
(i) an XRPD pattern substantially similar to that depicted in FIG. 15 ; (ii) a TGA pattern substantially similar to that depicted in FIG. 16 ; and (iii) a DSC pattern substantially similar to that depicted in FIG. 16 .
30 . The solid form according to claim 4 , wherein the solid form is characterized by one or more of the following:
(i) an XRPD pattern substantially similar to that depicted in FIG. 17 ; (ii) a TGA pattern substantially similar to that depicted in FIG. 18 ; and (iii) a DSC pattern substantially similar to that depicted in FIG. 18 .
31 . The solid form according to claim 4 , wherein the solid form is characterized by one or more peaks in its XRPD pattern selected from those at about 5.52, 9.60, 11.46, 13.66, and 20.13 degrees 2-theta.
32 . The solid form according to claim 4 , wherein the solid form is characterized by peaks in its XRPD pattern at about 5.52, 9.60, 11.46, 13.66, and 20.13 degrees 2-theta, corresponding to d-spacing of about 16.00, 9.21, 7.72, 6.48, and 4.41 angstroms, respectively.
33 . The solid form according to claim 4 , wherein the solid form is characterized by substantially all of the peaks (degrees 2-theta) in its XRPD pattern selected from
°2θ ± 0.2
5.52
9.60
10.85
11.46
12.93
13.66
15.60
16.07
16.52
18.39
19.36
20.13
21.60
22.29
23.12
24.16
25.35
26.97
30.03
31.95
32.71
34 . The solid form according to claim 4 , wherein the solid form is characterized by one or more of the following:
(i) an XRPD pattern substantially similar to that depicted in FIG. 19 ; (ii) a TGA pattern substantially similar to that depicted in FIG. 20 ; and (iii) a DSC pattern substantially similar to that depicted in FIG. 20 .
35 . The solid form according to claim 13 , wherein the solid form is characterized by one or more peaks in its XRPD pattern selected from those at about 9.42, 12.24, 17.40, 17.60, 17.80, and 18.22 degrees 2-theta.
36 . The solid form according to claim 13 , wherein the solid form is characterized by one or more peaks in its XRPD pattern selected from those at about 9.42, 12.24, 17.40, 17.60, 17.80, and 18.22 degrees 2-theta, corresponding to d-spacing of about 9.39, 7.23, 5.10, 5.04, 4.98, and 4.87 angstroms, respectively.
37 . The solid form according to claim 13 , wherein the solid form is characterized by substantially all of the peaks (degrees 2-theta) in its XRPD pattern selected from
°2θ ± 0.2
5.60
9.42
12.24
13.44
15.42
16.06
16.59
17.40
17.60
17.80
18.22
18.95
19.45
20.58
22.85
23.26
23.78
24.24
24.81
25.61
26.48
28.68
29.58
38 . The solid form according to claim 13 , wherein the solid form is characterized by one or more of the following:
(i) an XRPD pattern substantially similar to that depicted in FIG. 21 ; (ii) a TGA pattern substantially similar to that depicted in FIG. 22 ; and (iii) a DSC pattern substantially similar to that depicted in FIG. 22 .
39 . The solid form according to claim 1 , wherein X is maleic acid.
40 . The solid form according to claim 39 , wherein the solid form is crystalline.
41 . The solid form according to claim 40 , wherein the solid form is characterized by one or more peaks in its XRPD pattern selected from those at about 9.37, 10.10, 11.74, 14.89, 15.67, 15.91, 18.08, and 18.42 degrees 2-theta.
42 . The solid form according to claim 40 , wherein the solid form is characterized by peaks in its XRPD pattern at about 9.37, 10.10, 11.74, 14.89, 15.67, 15.91, 18.08, and 18.42 degrees 2-theta, corresponding to d-spacing of about 9.44, 8.76, 7.54, 5.95, 5.66, 5.57, 4.91, and 4.82 angstroms, respectively.
43 . The solid form according to claim 40 , wherein the solid form is characterized by substantially all of the peaks in its XRPD pattern selected from
°2θ ± 0.2
5.53
6.35
8.12
9.37
10.10
10.89
11.74
12.61
13.00
14.89
15.67
15.91
16.65
17.58
18.08
18.42
18.82
19.43
19.95
20.92
21.76
22.47
22.90
23.81
24.33
25.30
25.83
26.49
28.37
28.87
29.85
30.65
32.16
34.21
44 . The solid form according to claim 40 , wherein the solid form is characterized by one or more of the following:
(i) an XRPD pattern substantially similar to that depicted in FIG. 34 ; and (ii) a DSC pattern substantially similar to that depicted in FIG. 35 .
45 . The solid form according to claim 1 , wherein X is methanesulfonic acid.
46 . The solid form according to claim 45 , wherein the solid form is crystalline.
47 . The solid form according to claim 46 , wherein the solid form is characterized by one or more peaks in its XRPD pattern selected from those at about 9.53, 9.78, 16.47, 17.36, 19.48, and 20.12 degrees 2-theta.
48 . The solid form according to claim 46 , wherein the solid form is characterized by peaks in its XRPD pattern at about 9.53, 9.78, 16.47, 17.36, 19.48, and 20.12 degrees 2-theta, corresponding to d-spacing of about 9.28, 9.04, 5.38, 5.11, 4.56, and 4.41 angstroms, respectively.
49 . The solid form according to claim 46 , wherein the solid form is characterized by substantially all of the peaks in its XRPD pattern selected from
°2θ ± 0.2
5.70
7.75
9.53
9.78
10.55
10.93
11.53
12.07
13.05
13.50
13.75
14.08
14.27
14.96
15.87
16.47
16.79
17.36
17.97
18.84
19.18
19.48
19.68
20.12
20.49
21.39
22.10
22.75
23.28
23.97
24.66
27.09
27.75
29.45
31.30
32.81
50 . The solid form according to claim 46 , wherein the solid form is characterized by one or more of the following:
(i) an XRPD pattern substantially similar to that depicted in FIG. 36 ; and (ii) a DSC pattern substantially similar to that depicted in FIG. 37 .
51 . The solid form according to claim 1 , wherein X is p-toluenesulfonic acid.
52 . The solid form according to claim 51 , wherein the solid form is crystalline.
53 . The solid form according to claim 52 , wherein the solid form is characterized by one or more peaks in its XRPD pattern selected from those at about 9.72, 10.01, 11.16, 12.81, 17.58, and 18.20 degrees 2-theta.
54 . The solid form according to claim 52 , wherein the solid form is characterized by peaks in its XRPD pattern at about 9.72, 10.01, 11.16, 12.81, 17.58, and 18.20 degrees 2-theta, corresponding to d-spacing of about 9.10, 8.84, 7.93, 6.91, 5.05, 4.88 angstroms, respectively.
55 . The solid form according to claim 52 , wherein the solid form is characterized by substantially all of the peaks in its XRPD pattern selected from
°2θ ± 0.2
6.00
9.72
10.01
11.16
12.18
12.81
13.53
13.95
16.32
16.91
17.58
18.20
18.53
19.44
19.90
20.15
20.66
21.22
21.67
22.35
23.36
23.81
24.09
24.63
25.18
25.42
25.84
26.67
27.32
29.56
31.23
31.95
33.50
56 . The solid form according to claim 52 , wherein the solid form is characterized by one or more of the following:
(i) an XRPD pattern substantially similar to that depicted in FIG. 38 ; and (ii) a DSC pattern substantially similar to that depicted in FIG. 39 .
57 . A crystalline solid form of Compound 1:
58 . The solid form according to claim 57 , wherein the solid form is characterized by one or more peaks in its XRPD pattern selected from those at about 9.12, 12.31, 17.58, 18.12, and 19.19 degrees 2-theta.
59 . The solid form according to claim 57 , wherein the solid form is characterized by peaks in its XRPD pattern at about 9.12, 12.31, 17.58, 18.12, and 19.19 degrees 2-theta, corresponding to d-spacing of about 9.70, 7.19, 5.04, 4.90, and 4.63 angstroms, respectively.
60 . The solid form according to claim 57 , wherein the solid form is characterized by substantially all of the peaks (degrees 2-theta) in its XRPD pattern selected from
°2θ ± 0.2
5.55
6.81
9.12
10.56
12.31
13.78
15.35
16.54
17.58
18.12
19.19
20.77
22.78
24.34
26.51
29.45
30.24
61 . The solid form according to claim 57 , wherein the solid form is characterized by an XRPD pattern substantially similar to that depicted in FIG. 25 .
62 . The solid form according to claim 57 , wherein the solid form is characterized by one or more peaks in its XRPD pattern selected from those at about 7.69, 13.39, 14.64, 18.98, and 20.93 degrees 2-theta.
63 . The solid form according to claim 57 , wherein the solid form is characterized by peaks in its XRPD pattern at about 7.69, 13.39, 14.64, 18.98, and 20.93 degrees 2-theta, corresponding to d-spacing of about 11.50, 6.61, 6.05, 4.68, and 4.24 angstroms, respectively.
64 . The solid form according to claim 57 , wherein the solid form is characterized by substantially all of the peaks (degrees 2-theta) in its XRPD pattern selected from
°2θ ± 0.2
5.60
7.69
8.76
9.47
10.96
13.39
14.64
16.25
16.66
16.88
17.41
18.98
19.98
20.93
22.03
23.20
23.79
26.07
27.25
27.87
31.51
65 . A pharmaceutical composition comprising a solid form according to any one of claims 1 - 64 and a pharmaceutically acceptable carrier.
66 . A capsule composition comprising a solid form according to any one of claims 1 - 64 .
67 . The capsule composition of claim 66 , wherein the capsule composition comprises 100 mg Compound 1.
68 . The capsule composition of claim 66 , wherein the capsule composition comprises 200 mg Compound 1.
69 . The capsule composition of any one of claims 66 - 68 , wherein the capsule composition comprises Compound 1 with no excipients.
70 . A method of treating a disease associated with activity of platelet-derived growth factor receptors (PDGFR) and/or a vascular endothelial growth factor receptor, the method comprising administering to a patient in need thereof a solid form according to any of claims 1 - 64 .
71 . A method of treating a fibrotic disease or disorder, the method comprising administering to a patient in need thereof a solid form according to any of claims 1 - 64 .
72 . The method according to claim 71 , wherein the fibrotic disease or disorder is fibrosis.
73 . The method according to claim 72 , wherein the fibrosis is pulmonary fibrosis.
74 . The method according to claim 73 , wherein the pulmonary fibrosis is idiopathic pulmonary fibrosis (IPF).
75 . The method according to claim 72 , wherein the fibrosis is hepatic fibrosis.
76 . The method according to claim 72 , wherein the fibrosis is renal fibrosis.
77 . The method according to claim 71 , wherein the fibrotic disease or disorder is nephrotic syndrome or a disease, disorder, or condition associated with nephrotic syndrome.
78 . The method according to claim 77 , wherein the fibrotic disease or disorder is focal and segmental glomerulosclerosis (FSGS).
79 . The method according to claim 71 , wherein the fibrotic disease or disorder is primary glomerular disease.
80 . The method according to claim 71 , wherein the fibrotic disease or disorder is primary proteinuric kidney disease.
81 . The method according to claim 71 , wherein the fibrotic disease or disorder is membranous nephropathy.
82 . The method according to claim 71 , wherein the fibrotic disease or disorder is IgA nephropathy.
83 . The method according to claim 71 , wherein the fibrotic disease or disorder is FSGS.
84 . The method according to claim 72 , wherein the fibrosis is dermal fibrosis.
85 . The method according to claim 72 , wherein the fibrosis is gastrointestinal fibrosis.Join the waitlist — get patent alerts
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